In the central nervous system (CNS) the transmission of stimuli takes place by the interaction of a neurotransmitter, which is sent out by a neuron, with a neuroreceptor. L-glutamic acid, the most commonly occurring neurotransmitter in the CNS, plays a critical role in a large number of physiological processes. The glutamate-dependent stimulus receptors are divided into two main groups. The first main group forms ligand-controlled ion channels. The metabotropic glutamate receptors (mGluR) belong to the second main group and, furthermore, belong to the family of G-protein-coupled receptors.
At present, eight different members of these mGluRs are known and of these some even have sub-types. On the basis of structural parameters, the different second messenger signaling pathways and the different affinities to low-molecular weight chemical compounds, these eight receptors can be sub-divided into three sub-groups: mGlu1 and mGlu5 belong to group I, mGlu2 and mGlu3 belong to group II and mGlu4, mGlu6, mGlu7 and mGlu8 belong to group III.
Generally, these receptors function to modulate the presynaptic release of glutamate, and the postsynaptic sensitivity of the neuronal cell to glutamate excitation. The metabotropic glutamate receptors are useful targets for the treatment of acute and chronic neurological conditions and psychiatric disorders.
Ligands for the metabotropic glutamate receptors are described, for example, in EP 774 455. Compounds described therein are useful as modulators of metabotropic glutamate receptor function. These compounds differ from compounds of the present formula I by one or two substitutions on the ring molecule. The syntheses described for generically encompassed compounds are very uncertain and vague, and they lead to mixtures of diastereomers and/or enantiomers which would have to be separated into dean isomers by tedious and time-consuming procedures.